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International Herbal Conference 2009

Herbal Medicine – Evaluating of Quality, Efficacy and Safety in the changing global Scenario Bangalore, February 26 – 28, 2009

Approaching a new generation of novel Phytopharmaceuticals – Synergy-Research
Prof. H. Wagner
Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany
Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany

e-mail: h.wagner@cup.uni-muenchen.de

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Facts
 Of about 2000 registered acute and chronic diseases only

~40% are presently curable, a further ~40% diseases are only symptomatically or imperfectly treatable and ~20% not at all

 The resistance of pathogenic microorganisms against

antibiotics is increasing dramatically

 Of about 350000 plant species, including algae, protozoa,

fungi and bacteria only 20-30% have been investigated thoroughly and only 5-10% are used in Traditional Medicine

The paradigm "Monosubstance(drug) Therapy" failed, now gradually replaced by Multidrug and Multitarget-Therapy  Synergy Research mandatory
Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany
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Characteristic of novel Phytopharmaceuticals
 Standardized, more effective and causatively acting mono-

or multiherbal extracts

 Less or lacking side effects

 Applicable alone for therapy or in combination with

synthetic drugs or antibiotics

 Use also for the treatment of diseases which up to now were

reserved for the synthetic drugs or antibiotics only

Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany

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Which efforts are mandatory to achieve this goal?
 Appointment of national commissions

inventory of traditionally used medicinal plants to evaluate the medicinal plant resources of a country

 Development of Herbal Monographs with valuation of

quality, safety and efficacy of herbs and their extracts

 Integration of all modern high-tech analytical and molecular

biological methods inclusive omic technology

Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany

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German Commission E-Monographs as model
378 plants used in traditional medicine have been investigated to determine their quality, safety and efficacy 245 positive monographs of single plants and fixed combinations 133 negative or zero-monographs (not recommended for therapy, negative-benefit-risk rate)

Supplemented by ESCOP-, WHO and European Pharmacopoea-Monographs inclusive special Analytical Monographs

Novel Phytopharmaceuticals
Herbal medicinal products from traditional use Herbal medicinal products of well established use ("evidence-based medicine")
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or

Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .       thin-layer electrophoresis (TLE) Isotachophoresis (TIP) Capillary electrophoresis (CE) Capillary electrochromatography (CEC) HPLC. gas chromatography (GC) HPLC coupled with MS (chemical and ionization or electrospray ionization technique) Liquid chromatography (LC coupled with UV/MS/NMR/Fourier transform ion cyclotron resonance (FT-ICR)) Folie 6 Prof.High-tech analytical and isolation methods for plant screening and isolation work  Thin-layer chromatography (TLC). H.

Books for Fingerprint Analysis by Prof. Xiao Peigen Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 7 . H.

sinensis Z-Ligustilide. Xiao P. sinensis A. Wagner H. falcarindiol A.03. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 8 .96 Reference compounds + China. 2000 Anisaldehyde sulphuric acid reagent (VIS) 1 2 3 4 5 R 6 7 8 -Start Prof.07... pubescens -Front Koetzting 08. in press.M.G. linoleic acid.96 Kun Ming 12. H. sinensis A.TLC Fingerprint Analysis of Angelicae sinensis radix (Danggui) # 1 2 3 4 5 R Origin + Species A. authentic UV 254 nm 1 2 3 4 5 R 6 7 8 -Start -Front 7 8 9 UV 360 nm 1 2 3 4 5 R 6 7 8 -Start -Front Zschocke S. authentic China.. sinensis A.03. Bauer R.: Chinese Drug Monographs and Analysis. dahurica A. sinensis A. Kanton 12. authentic China.. Chen J.93 Singapore East Earth Herb Inc. acutiloba A.

Vol. Wagner H. 2(9). 1999 Prof. Bauer R. other species and adulterations 100 200 11 10 1 2 3 4 5 6 7 8 9 12 mAU Angelica pubescens Angelica dahurica Angelica apaensis Heracleum moellendorffii Heracleum candicans Aralia cordata 0 mAU 200 400 10 a b c Time (min) 20 g ef h k 30 h i j mAU 200 400 0 d a b 10 Time (min) 20 g e f j i 30 k 0 mAU mAU 200 400 0 200 400 10 c Time (min) 20 l n 30 k 10 o c Time (min) d 20 h i 30 k 0 mAU 0 200 400 10 Time (min) 20 30 k 10 Time (min) 20 30 Source: Liu Jianghua.HPLC Fingerprint Analysis of Angelicae pubescens radix (Duhuo). H. Xiao PG. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 9 . Chen JM: Chinese Drug Monographs and Analysis.

02 0.and HPLC-detection of Aristolochic acids in root samples of Stephania tetrandra Front Rƒ = 0.and Aristolochia root extracts Retention Time (min) Aristolochic acids detectable up to 400 pg Folie 10 Prof.and Aristolochia root extracts Aristolochic Start 1 2 3 4 T1/2 5 T3 6 7 acids detectable up to 8 pg/g Herbal drug Absorbance (AU) 0.06 0.Adulteration or mixups of the root of Stephania tetrandra (Hanfangji) with the root of Aristolochia fangchi (Guangfangji) HPTLC.5 1 . H.04 0.4: T1/2: 5: T3: 6 + 7: Stephania root extract Tetrandrine + Fangchinolin Aristolochic acids I + II Aristolochiae radix Mixtures of Stephania. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .00 0 5 10 15 20 25 30 25 30 1 3 2 3 50:50 and 80:20 mixtures of Stephania.

Differentiation of Codonopsis species by DNA fingerprinting 1 2 3 4 5 6 = Codonopsis pilosula = Codonopsis tangshen = Codonopsis modesta = Codonopsis nervosa = Campanumoea javania = Platycodon grandiflorus M = 100 bp mol. weight marker with a 800 bp intensive band PCR-RFLP patterns of rDNA ITS using restriction enzyme Hha I after separation by 3.5 % TBE agarose gel Fu et al.. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 11 . Planta Medica 65: 648-650 (1999) Prof. H.

radix  Paeoniae lactifl. Phytomedicine 8: 338-347 (2001) Prof.Composition of the Japanese herbal medicine Sho-seiryu-to extract (TJ-19)  Pinelliae pernatae tuber  Glyzyrrhizae glabrae radix  Cinnamomi cassiae cortex  Schisandrae chin. rhizoma Treatment of bronchitic asthma and allergic rhinitis Amagaya et al. radix  Ephedrae sin. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 12 . herba  Zingiberis offic. H. fructus  Asasari sieb.

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 13 . Amagaya et al.3 D HPLC fingerprint analysis of Sho-seiryu-to (TJ-19)extract produced from eight herbal drugs S. Phytomedicine 8: 338-347 (2001) Prof. H..

Omic Technology Bio-chip (photo by Miltenyi Biotec) Red: induction Green: repression Black: no differential regulation Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 14 . H.

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 15 . in the National Institute of Environmental Health Science (NIEHS) provides a reference system of genome wide gene expression data  the identification of the toxic potential of chemicals and plant extracts. Prof.Futural aspects of the omic technology for Phytomedicine  Complex mixtures cause multitarget effects on molecular base and lead to characteristic gene.and proteine expression profiles which are different of that of single compounds  synergistic effects  Simplification of the standardization process of herbal drug mixtures  consequences for legislation and patenting  The National Center for Toxicogenomics (NCT) in USA. H.

g. Anti-Hepatitis B + C)  Antiparasidal drugs Infectious diseases Inflammatory diseases (e. Leishmaniasis)  Antifungal drugs  Antiasthmatics  Drugs against bowle syndrom  Antineurodermitic / Antipsoriatic drugs Prof. H. Antituberculostatics)  Antiviral drugs (e. Anti-HIV.Development of novel Phytopharmaceuticals New drugs of high priority worldwide wanted Cancer  Therapeutics and preventives  Antihypertonics Antihypertonics Cardiovascular  Antiatherosclerotics diseases  Antiischemics (drugs for stroke prevention) CNS diseases Therapeutics and preventives for  Alzheimer disease  Parkinson  Antibacterial drugs (e. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 16 . against Malaria. Chagas.g.g.

H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 17 .High through put screening methods Thousands of plant extracts or pure compounds can be screened per month Prof.

H.Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 18 .

H.Traditional Medicine of many countries used herbal drug combinations from its very beginning Experiences  higher efficacy than a single herbal drug or constituent  less or lacking side effects  dose reduction possible Hypotheses  complex (multicausal) pathophysiology can be better positively influenced by a drug combination than by a single highly dosaged drug  more causative therapy possible  concomitant symptoms and damages also curable Conclusion: therapeutic superiority may be due to synergy.and multitarget effects Folie 19 Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .

hypertension-therapy) Prof.Synergy research as answer to the paradigm change in Drug Therapy Monosubstance Therapy Multidrug. H.Therapy (e. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 20 . AIDS-.and Multitarget. cancer-.g.

5 -3 0 10 20 30 40 50 60 weeks 0 10 20 30 40 50 60 weeks Zidovudin / Lamivudin / Delaviridin Zidovudin / Delaviridin Zidovudin / Lamivudin Folie 21 Prof.Comparison of the efficacy of different Anti-AIDS drug combinations Increase of helper-T-cells (cells / mm3) 120 100 80 60 40 20 Decrease of HIV-1 RNA in plasma (log10 -copies / ml) -0. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .5 -2 -2.5 -1 -1. H.

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 22 . Rev.1989)  A total effect of a combination is greater than expected from the sum of the individual agents E (da.db) > E (db) E = observed effect da and db = doses of agents a and b Prof.Definition of synergy effects (Berenbaum Pharmacol.db) > E (da) + E (db)  The effect of a combination is greater than that of each of the individual agents E (da. H.db) > E (da) and E (da. 41:93-141.

H.Pharmacological proof of synergy effects by the isobol method (Berenbaum 1985) Dose B an ta go ni ct io n ze ro sy n -in te ra sm er g is m Dose A  antagonism = negative interaction  synergism = positive interaction or potentiation  zero-interaction = effects-addition of individual components Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 23 .

Drug-synergism of phytopharmaceuticals plant extract one target different targets (multitargeting) overadditive. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany . potentiated pharmacological effects Folie 24 additive. agonistic pharmacological effects Prof. H.

60 2.42 1.40 1.29 Ginkgolide B [µM] 1.5 1 ze ro -in ter ac ti m 2 O O H O H O O O O H H O O H on O H O Ginkgolide B [µM] 2.20 1.5 1. H.80 1.5 IC50 – values for various dose-combinations of PAF-induced thrombocyte aggregation* GA : GB 3: 1 2: 1 1: 1 1: 2 1: 3 1 : 10 IC50 [µg/ml] 2.57 2.79 Folie 25 Prof.41 3.27 0.5 3 3.55 1.12 2.21 1.88 0.40 2.43 2.30 Ginkgolide A [µM] 4.Isobol measurements of Ginkgolide AB-combination* Ginkgolide A [µM] O O H H O O 14 12 10 8 6 O O O H O H H O O O O H 4 2 0 sy ne rg is 0.72 2. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 26 . H.What could be the causes of therapeutic superiority of many herbal drug combinations?  Synergistic multitarget action of extract constituents  Concomitant constituents increase the solubility and resorption rate and thereby the bioavailability of bioactive compounds (antibiotic drug) with resistance mechanism of pathogenic microorganisms  Interaction of one component of the drug combination  Elimination or "neutralisation" of adverse acting compounds by components of the drug combination Prof.

Major constituents of Hypericum perforatum extract HO OH O O Flavonoids (Rutin. Quercetin. H. Hyperoside. Tannins 2 – 15% Xanthones (traces) Prof. 13.18-Biapigenin) 5 – 12% Hyperforin (Adhyperforin) 1 – 7% Hypericin. Pseudohypericin 0.4% Procyanidins.1 – 0. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 27 .

3 Postsynaptic neuron Hypothalamus IL-6 Cortisol Adrenal cortex CRF TRH CRF _ Hypericin ACTH Prolactin Pituitary U.3. H.7 NK-I H1. Pharmacopsychiatry 34 Suppl. 1: 137-142 (2001) Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 28 . NMDA Hyperforin Hypericum Amentoflavon Estrogen _ 5-HT1A/2A DA2.. Simmen et al.118-Biapigenin Hypericum _ Sigma Opioid 5-HT6.4 GABAA Benzo Hyperforin Hypericum 13.Multitarget effects of Hypericum perforatum according to in vitro studies Presynaptic neuron COMT MAO _ H+ + Na + ? ? 5-H“ 5-H“ Flavonoids _ Xanthones + Hypericum _ β -adr.

L-glutamate) Prof.Multivalent pharmacological effects of Hypericum-extracts Chemistry: Hypericins. hyperforin. H. GABA. flavonoids. serotonin. procyanidins blockade of α 2-receptors modulation of β –receptorpacking     down regulation of 5-HT2-receptors Antidepressive Anxiolytic Nootropic Antiepileptic monoamine oxidase inhibition modulation of neurotransmitter concentrations (Nor-adrenalin. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 29 .

H.Arguments for existing synergy effects of Hypericum perforatum extracts I The accompanying procyanidin B2 and hyperoside of the hypericum extract increase the water solubility and oral bioavailability of hypericin by 58% / 34% as evidenced by the forced swim test (Porsolt test) 10 Hypericin [ng/ml] * Hypericin + procyanidinB2 * * Hypericin * 5 * 0 0 100 200 300 400 500 600 700 800 900 1000 1100 [min] Plasma levels of hypericin in the presence ( ) and absence ( ) of procyanidin B2 Butterweck et al. 69:189-192 (2003) Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 30 . Planta Med.

H.Tetrahydrocannabinol (THC) exerts polyvalent pharmacological activities antiphlogistic anxiolytic OH antiemetic analgesic O C 5H11 ∆ 9-THC muscle relaxing appetite stimulating sedative Folie 31 Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .

M. Nature 404:84-87. Baker et al.Pharmacological evidence for synergistic effects Percentage change in resistance to Flexion ± SEM 10 0 -10 -20 -30 -40 -50 0 10 20 30 40 50 60 Time (min) 70 80 90 P<0. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 32 . H. (2000). in E. Williamson Phytomedicine 8(5):401-404 (2001) Prof.002 by ANOVA ∆ 9Tetrahydrocannabinol (1mg/kg) Cannabis extract (5mg/kg) Containing 20% ∆ 9THC * * * * * * * # # * * * * * # # * * * Cannabis extract is a better antispastic agent in mice than tetrahydro-cannabinol (THC) at an equivalent dose.

(1994) Kimura et al. (1982) Baker et al. Chung et al. (1992) Miaorong and Jing (1996) Zuardi et al.In vitro and in vivo pharmacological evidences for synergy effects (according to Williamson.: Valeriana extract/ individual constituents Zingiber offic. (2000) Hölzl (1997) Beckstrom-Sternberg and Duke (1994) Capasso and Sorrentino (2005) Folie 33 Prof.: Zingiber extract/ mixture of volatile terpenoids and mixtures Kava-kava + Passiflora incarn. Phytomedicine 8(5):401-409 (2001) Ginkgo biloba: Ginkgolide mixtures/ Ginkgo extract Piper methysticum: Kava lactones/mixtures of Kava lactones and extract fractions Glycyrrhiza glabra: Licorice extract potentiates other substances and acts as detoxifier Cannabis sativa: Cannabis extract / THC Valeriana offic. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany . (1987) Singh and Blumental (1997) Cantelli-Forti et al. H.

H. Review Phytomedicine in press) Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 34 .Strategies of bacteria to antagonize the effect of antibiotics A Receptor or active site modification C penetration C* Decreased D Increased efflux A* D* B* B Enzymatic degradation or modification of antibiotic antibiotic drug receptor modified receptor efflux pump enzyme degradation of the drug (Mukesh Doble.

1 0 0.Synergistic effect of Pelargonium graveolens essential oil with Norfloxacin in inhibiting Staphylococcus aureus ATCC 6538 I A.5 0.6 Norfloxacin µg/ml 0.3 0.5 0.2 0.4 0.12 * FIC = Fractional inhibitory concentration ** FICI = FIC index = FIC of oil + FIC of Norfloxacin Folie 35 Prof.3 0. Phytomedicine 14:727 (2007) The isabole method describing synergy Staphylococcus aureus ATCC 6538 0.8 Pelargonium graveolens + Norfloxacin Pelargonium graveolens oil mg/ml FIC* = 0.6 Pelargonium graveolens oil mg/ml 0. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .2 0.1 0.37 Norfloxacin µg/ml FICI** = 0.25 FICI = 0. Rosato at al.4 0.7 0.

H.06 1. Phytomedicine 2006. 13:630-635 Prof.5 synergistic effect FIC = 1 additive effect FIC > 2 antagonistic effect  Results  7-MJ has superior extracellular and intracellular activity against M.Synergism between herbal and other drugs II Synergistic effects of 7-Methyl-Juglone (7-MJ) in combination with antituberculous drugs against Mycobacterium tuberculosis Intercellular MICs and FICs of combination of drugs acting against M. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 36 .007 FIC µg/ml – – – 0.t. tuberculosis by the radiometric BACTEC method MIC1) (µg/ml) and FIC2) of drugs and drug-combinations against M.25/0. relative to streptomycin The combination of 7-MJ with IN reduces the MICs of both compounds by eight-fold NB Bapela et al.125 0.5 0. tuberculosis H37Rv strain H37Rv 7-Methyl-Juglone (7-MJ) Rifampicin (RMP) Isoniazide (IN) 7-Methyl-Juglone + Rifampicin 7-Methyl-Juglone + Isoniazide 1) Minimum inhibitory concentration 2) Fractional inhibitory concentration MIC µg/ml 5 0.62/0.24 FIC ≤ 0.5 0.

4 ± 3. H.0 Days  Results  Combination of grape seed extract with Amp.2 ± 2. B dose of 0. Han Yongmoon Phytomedicine 2007. B results in a more than 75% reduction of Amp. B The MST value of the mice group which received the combination was greater than MST value from mice group given four times Amp.3 ± 8. Ref.4 14.4' 17. in press Prof.5mg/kg bw.Synergism between herbal and other drugs III Synergistic effects of Vitis vinifera seeds (grape seed extract = GSE) with amphotericin B (Amp) against disseminated Candidiasis in mice 5 4 Survivors MST (Days) DPBS Amp alone GSE alone Amp plus GSE 10 20 30 40 3 2 1 0 11.6' 38. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 37 .6 ± 7.

Phytomedicine 15: 639 .g. 1.652 (2008)) OH HO HO O HO O HO OH OH HO OH HO OH OH OH OH HO CO O OH HO HO CO O O CO O OC OH OH O CH2 O OH OH HO HO O O O 6 HO HO OH OH O OH OH OH OH O O 3 O Epigallocatechin gallate (EGCg) Corilagin Tellimagrandin I Natural products: e. Baicalin. Rugosin B. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 38 . Tea catechin. α -terpineol) + = Antibiotics: e.g. Ciprofloxacin. Erythromycin Modifiers of Multidrug resistance mechanisms Prof. Penicillin.Synergism between natural products and antibiotics against bacterial infection I (Hemaiswarya et al.8-cineol. Ampicillin.g. H.. Tetracycline. essential oil (e. Gentamicin. isoflavones. Plumbagin. Vanomycin.

Synergism between natural products and antibiotics against bacterial infection II (Hemaiswarya et al. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 39 . Phytomedicine 15: 639 .. H.652 (2008)) Isopimaric acid Carnosic acid Carnosol OH HO HOOC O CO2H O HO OH Prof.

Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 40 . H.Prof.

Amentoflavone. Procyanidines Imipramine: 3 x 25/35 mg Hypericum: Parameter: Hamilton-Depression Scale (HAMD) Vorbach et al. 1997 / Woelk 2000 Prof. Hyperforine. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 41 . H.Comparative double blind study with Hypericum extract and Imipramine Indication: moderate neurotic depression Score 25 20 15 10 5 0 1 2 4 6 Imipramine Li 160 Weeks Dosage: 3 x 300 mg extract /day ≅ 80-100 mg Hypericines.

Multitarget therapy of dyspepsia and motilityrelated disorders of the gastrointestinal tract with a combination of 9 plant extracts  Iberis amara (totalis)  Angelica archangelica (radix)  Matricaria chamomilla (flos)  Carum carvi (fruits)  Silybum marianum (fruits)  Melissa officinalis (folium)  Mentha piperita (folium)  Chelidonium majus (herba)  Glyzyrrhiza glabra (radix) Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 42 . H.

H.Clinical evidence of Iberogast®. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 43 . a multidrug phytopharmaceutical for the treatment of dyspepsia  12 clinical trials and 3 metaanalyses performed  Clinical studies in comparison with the prokinetics Metoclopramide® and Cisapride® Result: – Full therapeutic equivalence or superiority over the synthetic drugs – No or lesser side effects Prof.

Treatment of dyspepsia and motility-related disorders of the gastrointestinal tract with a herbal drug combination (Iberogast ®. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany . H. consisting of 9 plant extracts) Multiple mechanisms of the disease Iberis Angelica Carum Silybum Chelidonium Glycyrrhiza Chamomilla Melissa Mentha atonia hypo.hypermotility motility spasms acid secretion ulcus/ inflammation radical production Phytomedicine Suppl. V 13 (2006) none moderate strong effects Folie 44 Prof.

Option for Monotherapy Hypermotility Spasmolytic agent (Buscopan ®) Hypomotility Prokinetics (e. 5-HT-Antagonists) no standard therapy available Hypersensibility Hyper acid secretion proton pump inhibitor (e. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 45 . Metoclopramid ®. Omeprazol ®) Inflammation/Ulcus – Prof. H.g.g. Cisaprid ®.

H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 46 .Prof.

Trichophyton spec. Trichophyton spec. Candida albicans Candida albicans Candida albicans Folie 47 Prof. H. Agastache rugosa (estragole) Euphorbia characias Santolina oil Anethol Essential oil of Thymus vulgaris Synthetic drugs Ketaconazole Ketaconazole Ketaconazole Ketaconazole Clorimazole Miconazole Amphotericin β Fungal species Trichophyton spec. Phytomedicine 15: 639 .Combination of natural products and synthetic drugs to combat fungal infections (Hemaiswarya et al.. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany .652 (2008)) Natural products Allium sativum Essential oils of Peucedanum grav. Trichophyton spec.

artemisinin derivatives combined with lumefantrine or doxycycline and mefloquine combined with tetracycline or doxycycline have been evaluated with improvement of the cure rate in uncomplicated malaria  Artemisinin derivatives intravenously or intrarectally combined with mefloquine may be alternatives to intravenous quinine for treatment of severe malaria Arch. 33: 416 . H. Res. Med.Future Outlook of Antimalaria Drugs  Malarone®. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 48 .421 (2002) Prof.

H.Futural multitarget therapy I Example 1: Cancer therapy immunostimulants healthy tissue inhibitors of angiogenesis cytostatics stimulants of oncogen-suppressor genes cancer cells inducers of apoptosis Prof. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 49 .

Futural multitarget therapy II Example 2: Therapy of Hepatitis B+C immunostimulants antioxidants antifibrotics antiinflammatory drugs HBV/HCV inhibitors of apoptosis liver protecting agents Liver Virostatic drugs Prof. H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 50 .

synergy research and omic technology can give phytotherapy a new legitimacy and the possibility to treat diseases which up to now were reserved for chemotherapy only Prof. H. molecular biology. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 51 .Conclusion Progress in the field of high tech analysis.

H. Wagner – Center of Pharmacy Research – Pharmaceutical Biology – University of Munich – Germany Folie 52 .Prof.